This invention relates to a process for preparing a 2-alkyl-4-amino-5-aminomethylpyrimidine. More particularly, it relates to an improved process for preparing 2-alkyl-4-amino-5-aminomethylpyrimidine by reductive amination of a 2-alkyl-4-amino-5-formylpyrimidine with ammonia and hydrogen.
It is known that 2-alkyl-4-amino-5-aminomethylpyrimidine is an important intermediate compound for synthesis of vitamin B.sub.1 and its analogous compounds.
In general, it has been known in the art to produce a primary amine such as 2-alkyl-4-amino-5-aminomethylpyrimidine by reductive amination of an aldehyde such as 2-alkyl-4-amino-5-formylpyrimidine with ammonia and hydrogen. The reaction routes are considered to be represented by the following reaction scheme: ##STR1## As can be seen from said reaction routes, it has been estimated that an aldehyde [I] is first iminated to form an aldimine [II] as the intermediate, followed by hydrogen reduction, to give a desired primary amine [III] such as 2-alkyl-4-amino-5-aminomethylpyrimidine.
In the prior art, said reaction has been practiced by dissolving an aldehyde of the starting material in an inert solvent and blowing simultaneously ammonia and hydrogen into the solution in the presence of a reducing catalyst, as disclosed in Japanese Unexamined Patent Publication. (KOKAI) No. 140079/1983, thereby producing resultant products in an yield of from about 80 to 90%. However, other than the desired primary amine, a number of by-products, primary alcohols, secondary and tertiary amines represented by the above [IV] to [VII] such as 2-alkyl-4-amino-5-hydroxymethylpyrimidine and di-(2-alkyl-4-amino-5-pyrimidylmethyl)amine are formed in large amounts, whereby the yield and the selectivity of the primary amine such as 2-alkyl-4-amino-5-aminomethylpyrimidine are very low. As a measure to cope with this problem, there has been only a proposal to control the amount of ammonia relative to the aldehyde of the starting material.
For example, according to JACS 61 3566 (1939), in the case of an aldehyde having no active hydrogen on .alpha.-carbon such as benzaldehyde, a primary amine is disclosed to be formed preferentially in an alcoholic solution of ammonia by controlling the molar ratio of the aldehyde to ammonia. However, even in the process according to this proposal, the yield of the primary amine is 80 to 90%, with the secondary amine being by-produced at a yield of 6 to 16%.